Clinical outcome of Japanese metastatic colorectal cancer patients harbouring the KRAS p.G13D mutation treated with cetuximab + irinotecan.

OBJECTIVE Metastatic colorectal cancer with KRAS codon 12 or 13 mutations is not currently treated with anti-epidermal growth factor antibodies. A recent retrospective study in Western countries raised the possibility that KRAS p.G13D mutation may not be absolutely predictive of non-response compared with other KRAS mutations from the findings of longer overall survival and progression-free survival following cetuximab treatment. We retrospectively investigated the relationship between KRAS status and cetuximab efficacy among Japanese patients. METHODS Data of 109 patients from nine institutions in Japan were retrospectively analysed. All patients were refractory or intolerant to fluoropyrimidine, oxaliplatin and irinotecan, and they were treated with a cetuximab + irinotecan regimen. The response rate, disease control rate, progression-free survival and overall survival were compared according to KRAS status. RESULTS Overall, 76 (70%), 7 (6%) and 26 (24%) patients had KRAS wild-type, KRAS p.G13D and other KRAS mutations. Their various parameters were as follows: response rate: 30% (23/76), 14% (1/7) and 0% (0/26); disease control rate: 71% (54/76), 71% (5/7) and 54% (14/26); median progression-free survival: 4.6 months (95% confidence interval, 2.8-6.3), 4.1 months (0-9.9) and 2.1 months (1.5-2.8); and median overall survival: 11.2 months (6.4-16.0), 8.5 months (5.3-11.8) and 6.8 months (4.1-9.6), respectively. CONCLUSIONS Although no statistically significant difference in progression-free survival or overall survival was observed between KRAS p.G13D-mutant and other mutant tumours, the disease control rate was higher in KRAS p.G13D-mutant patients and a partial response was observed in one such patient. Our study suggested that cetuximab showed some activity in KRAS p.G13D-mutant colorectal cancer patients. Further research is warranted.